In the pharmaceutical industry, there has long been a need to fill sterile drug products, such as solutions, suspensions, gels, ointments, and powders into sterile containers, such as vials, pre-filled syringes, plastic eye-drop bottles, or IV bags.
In some instances, sterility of the drug product has been achieved by first filling the drug into vials or bottles, and then sterilizing the filled containers by exposure to steam, such as in an autoclave, or by exposing the product to sterilizing doses of radiation. However, in many cases, the product, by it's nature, may be damaged by exposure to extreme heat or radiation and therefore cannot be sterilized by these methods. In these circumstances, sterility may be achieved by the process of sterilizing the drug product and the vials or bottles separately, and by then filling the sterile drug product into the sterile containers in a cleanroom environment, also known as an aseptic environment. The process of filling sterile product in an aseptic environment is often termed an aseptic filling operation.
Historically, there are several types of cleanrooms, or aseptic environments that have been used for the filling of sterile drug products. One type accommodates human operators working directly in the filling room. In these traditional cleanrooms, an aseptic environment is achieved through the combination of the constant circulation of sterile-filtered air, the maintenance of higher air pressure in the filling room than in the adjacent rooms, the periodic sanitization of the room and the filling equipment within the room, the sterilization of the drug product and the containers prior to entry into the room, and the gowning of the people working in the room with sterile outer garments.
Another type of environment that is often used for filling small quantities of sterile drug product is the laminar flow workbench, or laminar flow hood. A laminar flow workbench provides a localized aseptic environment through the continuous flow of sterile air. When small quantities of sterile containers are to be filled, such as in certain research settings, or in some compounding pharmacies, it has been known for a technician, wearing sterile gloves and gown, to introduce a bag of pre-sterilized containers onto the surface of the laminar flow workbench, and to then fill pre-sterilized drug product into the sterile containers, and to subsequently stopper, cap or seal the containers in the aseptic environment of the laminar flow air.
Another type of environment for aseptic filling is an isolator with glove-box fittings. In an isolator human operators do not physically enter the enclosure. Rather, they are able to perform manipulations from outside the enclosure by reaching into the isolator with the use of integral sterile gloves or integral isolator suits, which provide a barrier between the person performing the manipulation and the sterile environment inside the isolator. The isolator is decontaminated with an antimicrobial gas or vapor, often the gas being vaporized hydrogen peroxide. Sterility of the environment is maintained by keeping the isolator closed and by circulating sterile-filtered air through the isolator. The empty containers to be filled are normally sterilized externally to the isolator and are then introduced into the isolator through a docking port, or rapid transfer port, that allows for sterile transfer from one sterile enclosure into another.